Interfering with VE-PTP stabilizes endothelial junctions in vivo via Tie-2 in the absence of VE-cadherin

• DOI: 10.1084/jem.20150718
• Publication Date: 2015-12-08T16:08:16Z
• Authors: Maike Frye; Martina Dierkes; Verena Küppers; Matthias Vockel; Janina Tomm; Dagmar Zeuschner; Jan Rossaint; Alexander Zarbock; Gou Young Koh; Kevin Peters; Astrid Fee Nottebaum; Dietmar Vestweber
• Keywords: VE-cadherin

Vascular endothelial (VE)–protein tyrosine phosphatase (PTP) associates with VE-cadherin, thereby supporting its adhesive activity and junction integrity. VE-PTP also Tie-2, dampening the kinase of this receptor that can support stabilization junctions. Here, we have analyzed how interference affects stability junctions in vivo. Blocking by antibodies, a specific pharmacological inhibitor (AKB-9778), gene ablation counteracted vascular leak induction inflammatory mediators. In addition, leukocyte transmigration through barrier was attenuated. Interference Tie-2 expression vivo reversed junction-stabilizing effects AKB-9778 into junction-destabilizing effects. Furthermore, lack sufficient to weaken vessel barrier. Mechanistically, inhibition stabilized via which triggered activation Rap1, then caused dissolution radial stress fibers Rac1 suppression nonmuscle myosin II. Remarkably, VE-cadherin did not abolish effect inhibitor. Collectively, conclude stabilizes challenged VE-cadherin–independent mechanism. absence however, destabilizes integrity agreement VE-cadherin–supportive VE-PTP.